Increased risk of obesity in sons of women with PCOS

Results from a study by Karolinska Institutet researchers show that sons of women with polycystic ovary syndrome (PCOS) are three times more likely to be obese. The team made observations through evaluation of human registry data and the results of clinical case-control studies. The researchers then confirmed their findings ly in male offspring of mothers exposed to diet-induced obesity and/or dihydrotestosterone during pregnancy.

“Through these experiments, we can show that obesity and high levels of male hormones in pregnant women can cause long-term health problems in male offspring. It reduces reproductive function and affects future generations,” said Dr. Qiaolin Deng, associate professor in the Department of Physiology and Pharmacology at the Karolinska Institutet.

The team said the study’s findings highlight a previously unknown risk of PCOS-related health problems being passed on through generations through the male side of the family. Cell Report Medicine (“Intergenerational transmission of reproductive and metabolic dysfunction in male offspring with polycystic ovary syndrome“Our study now provides evidence that sons with PCOS have altered lipid profiles and are at increased risk for childhood obesity.”

PCOS is caused by the ovaries producing too much of the sex hormone testosterone. The disease affects approximately 15% of women of childbearing age worldwide and can make pregnancy difficult. Additionally, the disease is associated with various health problems, including diabetes and mental illness. More than 50% of women with PCOS are obese.

Daughters of women with PCOS have five times the risk of developing the same disease, and while it is not yet clear how sons of women with PCOS (PCOS-sons) are affected, studies show that weight and hormone levels “Although the clear phenotype of male offspring associated with PCOS has not yet been defined, sons born to mothers with PCOS have a body mass index show prepubertal signs of reproductive dysfunction with increased body mass index (BMI), insulin resistance, and increased anti-Müllerian (AMH) hormone levels, showing increased Sertoli cell numbers,” the researchers said. I am writing.

In the reported study, researchers used both registry data and mouse models to determine whether and how PCOS-like traits are passed from mother to son. Their previous findings showed that PCOS-sons had increased BMI and abnormal glucose and lipid metabolism. increased and reduced testicular volume,” the team noted.

To follow these findings in a large cohort, the researchers conducted a national Swedish registry-based cohort study to investigate whether sons with PCOS were more likely to be diagnosed with obesity. bottom. Over 460,000 of her sons born in Sweden between July 2006 and her December 2015 were included in the registry survey. About 9,000 of these were sons of women with PCOS. Researchers then identified which children were obese. The team also used data from a longitudinal case-control study from Chile.

“We found that sons of women with PCOS had three times the risk of obesity and high levels of ‘bad’ cholesterol. This increases the risk of developing insulin resistance and type 2 diabetes later in life,” said lead researcher Elisabet Stener-Victorin, Ph.D., professor of physiology and pharmacology at the Karolinska Institutet.

These findings were confirmed in an mouse study. In this study, female mice were fed either a standard diet or a diet rich in fat and sugar before and during pregnancy. Some mothers were also exposed to high levels of the male hormone dihydrotestosterone during pregnancy. These four groups of women mimicked pregnancies in normal-weight women, obese women, normal-weight women with PCOS, and obese women with PCOS.

The male offspring of these mothers were fed a standard diet until adulthood, after which they were examined for fat distribution and metabolism.The male offspring of the PCOS model mothers gained more weight. “F1 male offspring of the androgenic, androgenic and obese strains, respectively, gained weight,” the authors said. “We found that these male mice had more adipose tissue, larger adipocytes, and a disturbed basal metabolism, even though they were on a healthy diet,” he says. said.

To investigate whether offspring reproductive function and physiological characteristics are inherited from generation to generation, first-generation (F1) male mice were exposed to male sex hormones and a fatty diet. Not mated with healthy female mice. and sugar. This whole process was repeated in the second generation (F2), until we reached the third generation (F3). This was the first generation of mothers found to be unaffected by her PCOS. “Both the F1 and F3 male offspring of the androgenic and obese strains, respectively, had higher fat mass.” With or without diet-induced obesity, androgenic PCOS-like mouse models confirmed that reproductive and metabolic dysfunctions in offspring of F1 males were inherited in F3. ”

They also found changes in small noncoding RNAs in the sperm of male offspring three generations ago. These results suggest that “prenatal androgen exposure and/or maternal obesity are associated with a common DEsncRNA (i.e., transgenerational DEsncRNA) in the sperm of F1, F2, and F3 offspring for reproduction to F3 male offspring.” and the transfer of metabolic traits.” …Furthermore, we found that several DEsncRNAs in the serum of PCOS-sons were shared with his DEsncRNAs across generations in mouse sperm, highlighting the translational relevance of our cross-generational mouse studies doing. ”

Daughters of women with PCOS are five times more likely to be diagnosed with PCOS, and the team’s recent study found that offspring of first-generation males exposed to prenatal androgens develop abnormal reproductive and metabolic phenotypes. Together with the results, they suggested, “This strengthens the hypothesis that maternal PCOS induces fetal programming, and that unfavorable maternal and fetal environments predispose not only daughters but also sons to adult diseases.

“These findings highlight the risk of transmitting health problems to the male side of the family, highlight the risks of transmitting this type of health problem, and could help us find ways to identify, treat and cure in the future. It is important because it is toxic and prevents reproductive and metabolic diseases early,” said Stener-Victorin.

“Together, our comprehensive analysis defines the long-term adverse effects of gestational obesity and prenatal androgen excess, resulting in transgenerational transmission of metabolic and reproductive traits in male offspring.” “Importantly, several molecular features were detectable in the sera of PCOS sons, supporting the possibility of epigenetic inheritance in humans.” , reinforces the translational importance identified in the mouse model and sheds light on the previously underappreciated risk of transgenerational reproductive and metabolic alterations through the male germline.”